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| | {{STRUCTURE_4cd2| PDB=4cd2 | SCENE= }} | | {{STRUCTURE_4cd2| PDB=4cd2 | SCENE= }} |
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| - | '''LIGAND INDUCED CONFORMATIONAL CHANGES IN THE CRYSTAL STRUCTURES OF PNEUMOCYSTIS CARINII DIHYDROFOLATE REDUCTASE COMPLEXES WITH FOLATE AND NADP+'''
| + | ===LIGAND INDUCED CONFORMATIONAL CHANGES IN THE CRYSTAL STRUCTURES OF PNEUMOCYSTIS CARINII DIHYDROFOLATE REDUCTASE COMPLEXES WITH FOLATE AND NADP+=== |
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| - | ==Overview==
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| - | Structural data from two independent crystal forms (P212121 and P21) of the folate (FA) binary complex and from the ternary complex with the oxidized coenzyme, NADP+, and recombinant Pneumocystis carinii dihydrofolate reductase (pcDHFR) refined to an average of 2.15 A resolution, show the first evidence of ligand-induced conformational changes in the structure of pcDHFR. These data are also compared with the crystal structure of the ternary complex of methotrexate (MTX) with NADPH and pcDHFR in the monoclinic lattice with data to 2.5 A resolution. Comparison of the data for the FA binary complex of pcDHFR with those for the ternary structures reveals significant differences, with a >7 A movement of the loop region near residue 23 that results in a new "flap-open" position for the binary complex, and a "closed" position in the ternary complexes, similar to that reported for Escherichia coli (ec) DHFR complexes. In the orthorhombic lattice for the binary FA pcDHFR complex, there is also an unwinding of a short helical region near residue 47 that places hydrophobic residues Phe-46 and Phe-49 toward the outer surface, a conformation that is stabilized by intermolecular packing contacts. The pyrophosphate moiety of NADP+ in the ternary folate pcDHFR complexes shows significant differences in conformation compared with that observed in the MTX-NADPH-pcDHFR ternary complex. Additionally, comparison of the conformations among these four pcDHFR structures reveals evidence for subdomain movement that correlates with cofactor binding states. The larger binding site access in the new "flap-open" loop 23 conformation of the binary FA complex is consistent with the rapid release of cofactor from the product complex during catalysis as well as the more rapid release of substrate product from the binary complex as a result of the weaker contacts of the closed loop 23 conformation, compared to ecDHFR.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_10194348}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 10194348 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_10194348}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Folate]] | | [[Category: Folate]] |
| | [[Category: Oxido-reductase]] | | [[Category: Oxido-reductase]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 22:21:53 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Jul 3 13:31:28 2008'' |
Revision as of 10:31, 3 July 2008
Template:STRUCTURE 4cd2
LIGAND INDUCED CONFORMATIONAL CHANGES IN THE CRYSTAL STRUCTURES OF PNEUMOCYSTIS CARINII DIHYDROFOLATE REDUCTASE COMPLEXES WITH FOLATE AND NADP+
Template:ABSTRACT PUBMED 10194348
About this Structure
4CD2 is a Single protein structure of sequence from Pneumocystis carinii. Full crystallographic information is available from OCA.
Reference
Ligand-induced conformational changes in the crystal structures of Pneumocystis carinii dihydrofolate reductase complexes with folate and NADP+., Cody V, Galitsky N, Rak D, Luft JR, Pangborn W, Queener SF, Biochemistry. 1999 Apr 6;38(14):4303-12. PMID:10194348
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